Epoxides, also known as oxiranes, are useful intermediates in synthesizing active pharmaceutical ingredients and drugs. The inherent polarity and strain of the three-membered ring makes them susceptible to reaction with a large number of reagents. Of particular interest is the stereoselective nucleophilic attack of the epoxide ring to form 1,2-di-substituted products.
Δ9-Tetrahydrocannabinol (THC) is one of the biologically active components of cannabis. Pharmaceutical interest in THC has increased due to FDA approval for several therapeutic applications. Many of the known processes for the preparation of THC utilize (+)-p-mentha-2,8-diene-1-ol or an analog thereof as an intermediate. The (+)-p-mentha-2,8-diene-1-ol or an analog can be prepared from limonene through a synthesis that includes opening an epoxy ring. Conventional methods for converting limonene into (+)-p-mentha-2,8-diene-1-ol include oxidizing limonene with singlet oxygen and conversion using an enzymatic reaction.
Previous methods to synthesize (+)-p-mentha-2,8-diene-1-ol present certain drawbacks when attempts are made to produce on a commercial scale. Many of these methods result in the formation of significant isomeric mixtures of intermediates and the final product, requiring chiral resolution. Previous methods are therefore too costly and/or complicated to scale up to commercial scale. To this date there is no known commercial process for the production of (+)-p-mentha-2,8-diene-1-ol or its' analogs.
It is therefore desirable to provide a regio- and stereoselective process for opening an epoxide ring, thereby providing a regio- and stereoselective process for preparing (+)-p-mentha-2,8-diene-1-ol.